ABSTRACT A High School Program for Preventing Prescription Drug Abuse This Fast-Track SBIR proposal is designed to address the critical need for an effective primary prevention approach for prescription drug abuse (PDA), an urgent public health crisis in the United States. Deaths from prescription drug overdoses have more than tripled in the past 15 years, and the abuse of prescription opioids has fueled a dramatic rise in heroin abuse, with 3 of 4 new heroin users reporting a history of misuse of prescription opioids. The peak ages for PDA in the U.S. are 18 to 25. Thus, effectively preventing PDA in adolescents is central to reducing further increases in morbidity and mortality. Research demonstrates that alcohol, marijuana, and other forms of substance abuse typically co-occur with PDA and share similar risk and protective factors. School-based prevention provides access to large numbers of youth, but new program implementation modalities are needed because there is less time available for classroom-based prevention than in years past. Thus, there is a need for prevention programs that address the risk and protective factors unique to PDA, are broad-based in nature so that they address the risk and protective factors common to substance abuse and related problem behaviors, incorporate best practices in effective substance abuse prevention, and take advantage of new technologies to enhance classroom-based sessions. In the proposed project, we will develop and test an adaptation of the evidence-based substance abuse prevention approach called Life Skills Training (LST). The LST program has been extensively tested and found to effectively prevent substance abuse, violence and aggression in a series of randomized controlled trials with behavioral effects reported in over 30 peer-reviewed publications. The proposed preventive intervention for high school PDA will (1) utilize both online e-learning modules and interactive classroom sessions to address PDA and concurrent alcohol/drug abuse; (2) positively change social norms surrounding PDA and alcohol/drug abuse; (3) challenge positive expectancies about the benefits of PDA; (4) discourage diversion of prescription medication; (5) enhance protective factors by building social, self-regulation, and relationship skills through interactive learning and behavioral rehearsal scenarios; and (6) include online booster sessions. In Phase I, we will focus group test prototype materials with high school students, teachers, and administrators to demonstrate feasibility, relevance, usefulness, and appeal. Materials will be revised based on focus group feedback. In Phase II we will fully develop the program materials and conduct a rigorous national randomized trial of the prevention program. High schools (N=30) will be randomized into either an intervention group that receives the intervention or a treatment-as-usual control group that receives existing school health education programming. At the end of the initial intervention period, and at one- and two-year follow-ups, we will compare both groups with respect to changes in behaviors, norms, attitudes, and knowledge regarding PDA and other forms of substance abuse. This research offers the potential to identify an innovative and engaging prevention program capable of reducing PDA and other drug abuse.